Conclusion
These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND.
Results
SHR/ND were treated with vehicle (nU10), cilnidipine [33 mg/kg per day, orally (p.o.); nU11] or amlodipine (20 mg/kg per day, p.o.; nU9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters.